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Author:    Donna Thomas (RN, MSN, BSHEd)

Objectives

After completing this course, the learner will be able to:

  • Identify the difference between the clinical presentation of commonly seen influenza-like illness (ILI) and Anthrax.
  • Identify the Epidemiologic Considerations.
  • Identify testing procedures for Anthrax.
  • Identify the elements in an investigation and response to a bacillus anthracis (the organism that causes anthrax) exposure.

Distinguishing Influenza-Like Illness from Inhalation Anthrax

The presentation of inhalation anthrax is similar to the presentation of Influenza-like Illness (ILI). ILI is a nonspecific respiratory illness characterized by fever, fatigue, cough and other symptoms. Most ILI cases are not cause by influenza, but by other viruses like rhinoviruses, respiratory syncytial virus (RSV), adenoviruses and parainfluenza viruses. Other less common causes of ILI are bacterial, like Legionella spp., Chlamydia pneumoniae, Mycoplasma pneumoniae and Streptococcus pneumoniae. 3 Adults average 1-3 ILI per year. Children average 3-6 ILI per year. 7

Clinicians should consider a combination of epidemiologic, clinical and if indicated, lab and radiology test results to evaluate the likelihood that inhalational anthrax is the basis for ILI symptoms.

 

Clinical Considerations

Certain sign and symptoms help distinguish inhalational anthrax from other causes of ILI. Nasal congestion and rhinorrhea are symptoms of most ILI infections that are not associated with Anthrax. 8-9 Rhinorrhea was reported in only one of the 10 cases of inhalational anthrax diagnosed since September 2001. All 10 patients with inhalational anthrax had abnormal chest x-rays on initial presentation. 7 had mediastinal widening, 7 had infiltrates and 8 had pleural effusion. These findings are more discernable on posteroanterior with lateral views than on anteroposterior views done by a portable x-ray machine. 3

The initial illness in these patients was characterized by fever (nine) and/or sweats/chills (six). Severe fatigue or malaise was present in eight and minimal or nonproductive cough in nine, including one with blood-tinged sputum. Eight patients reported chest discomfort or pleuritic pain. Abdominal pain or nausea or vomiting occurred in five, and five reported chest heaviness. Other symptoms included shortness of breath (seven), headache (five), myalgias (four), and sore throat (two). 3

Most cases of ILI are not associated with x-ray findings of pneumonia, which occurs most often among the very young, elderly or those with chronic lung disease. 4-5 Influenza associated pneumonia occurs in approximately 1%-5% of community-dwelling adults with influenza and can occur in more than 20% of influenza-infected elderly. 4 Influenza-associated pneumonia might be caused by the primary virus infection, or more commonly, by bacterial infection occurring coincidental with or following influenza infection. 4

Epidemiologic Considerations

As of October, 2001, 10 confirmed cases of inhalational anthrax had been identified. 3 The epidemiologic profile of these 10 cases caused by bioterrorism can guide the assessment of persons with ILI. All but one case occurred among postal workers, persons exposed to letters or areas know to be contaminated by anthrax spores and media employees. The 10 confirmed cases have been identified in a limited number of communities. Inhalational anthrax is not spread from person to person. In comparison, millions of ILI cases associated with other respiratory pathogens occur each year and are found in all communities.

Respiratory infections associated with bacteria can occur throughout the year. Pneumococcal disease peaks during the winter. Mycoplasma and legionellosis are more common during the summer and fall. 6 Cases of ILI resulting from influenza and RSV generally peak during the winter. Rhinoviruses and parainfluenza virus infections usually peak during the fall and spring. Adenovirus circulates through the year. 2 All of these viruses are highly communicable and spread easily from person to person.

 

Testing

There are no rapid screening tests available to diagnose inhalational anthrax in the early stages. Blood cultures grew bacillus anthracis in all 7 patients with inhalational anthrax, who had not received previous antimicrobial therapy. However, blood cultures should not be obtained routinely on all patients with ILI symptoms, who have no probable exposure to anthrax. They should be obtained in situations where bacteremia is suspected.

Rapid tests for influenza and RSV are available. If used, these should be conducted within the first 3-4 days of a person’s illness, when viral shedding is most likely. RSV antigen detection tests have a peak sensitivity of 75%-95% in infants but do not have enough sensitivity to warrant their routine use among adults. 10

The clinical usefulness of rapid influenza tests is limited because the sensitivity of the influenza rapid tests is relatively low (45%-90%), and a large proportion of people with influenza might be missed with these tests. Therefore, the rapid influenza tests should not be done on every person presenting with ILI. However, rapid influenza testing used with viral culture can help indicate whether influenza viruses are circulating among specific populations, like a nursing home, or a school. This type of epidemiologic information on specific populations can aid in diagnosing ILI.

Vaccination against influenza is the best method to prevent influenza and its severe complications. The vaccine is targeted toward health-care workers to prevent transmission of influenza to high-risk persons. In addition, vaccination is recommended for household members of high-risk persons and for healthy persons aged 50-64 years.

The vaccine can prevent 70%-80% of influenza infections in healthy adults.2 Therefore, receipt of the flu vaccine will not definitely exclude influenza from the differential diagnosis of ILI or increase the probability of inhalational anthrax as a cause, especially among persons who have no probable exposure to anthrax. The vaccine does not prevent ILI caused by infectious agents other than influenza. Frequent hand washing can reduce the number of respiratory illnesses 12 and pneumococcal polysaccharide vaccine can reduce the risk for serious pneumococcal disease.

Investigation and Response to Bacillus Anthracis Exposure

Environmental Sampling

Sampling or testing the surfaces and air in an environment can be used to detect bacillus anthracis when investigating an exposure. The highest priority of an investigation is to evaluate the risk for exposure to aerosolized bacillus anthracis spores. Care should be taken by the person collecting test samples to obtain adequate samples; avoid cross-contamination during processing; and ensure proficient laboratory testing and interpretation of the test results. When bacillus anthracis is found in a sample of an environmental surface, it may be caused by cross-contamination from an exposure vehicle (e.g. contact with an envelope containing bacillus anthracis), background occurrence of the spores in the environment, or previously aerosolized bacillus anthracis that has settled onto environmental surfaces. Test results of environmental surface samples should not be the only criterion for starting, continuing or stopping antimicrobial prophylaxis for inhalational disease.

Environmental sampling can be directed, prospective or random. In directed sampling, test samples are obtained as part of an investigation of a specific threat, known exposure or of persons with bioterrorism-related anthrax. This type of sampling may play a critical rile in characterizing potential exposures and guiding public health action.

Prospective environmental sampling is an ongoing sampling and testing for bacillus anthracis. The value of prospective sampling is unknown. Current technology for monitoring air for bacillus anthracis and other agents are not validated and their performance has not been assessed during bioterrorism events. Prospective environmental sampling of surfaces may have a role in detecting bacillus anthracis contamination, especially at facilities or events determined to be a high risk for bioterrorism.

Random environmental sampling is of uncertain utility in detecting past exposures. Positive results from random sampling may represent cross-contamination from an exposure vehicle (e.g. letter) that poses negligible risks for inhalation anthrax. The positive test results may prompt more extensive evaluation to direct clean up, if needed.

Nasal Swab Cultures

Nasal swab cultures should not be used to diagnose cases of anthrax or to evaluate whether a person has been exposed. Nasal swab cultures may be useful in the investigation of known or suspected airborne bacillus anthracis. Because the sensitivity of nasal swab cultures decreases over time, cultures should be obtained within 7 days of the exposure. The presence of bacillus anthracis from a nasal swab culture cannot be determined by gram stain or colony characteristics alone and requires confirmatory testing by qualified laboratories.

Antimicrobial Prophylaxis

Antimicrobial prophylaxis is used to prevent inhalation anthrax. Prophylaxis is often started before the extent of exposure is known. Subsequent epidemiological and laboratory test data may indicate that some people started on prophylaxis were not exposed. These people should stop antimicrobial prophylaxis. People who were exposed should complete 60 days of therapy. No shorter course of antimicrobial prophylaxis exists. The choice of an antimicrobial agent should be based on antimicrobial susceptibility, the drug’s effectiveness, adverse events and costs. Bacillus anthracis isolates from people with bioterrorism-relate anthrax have been susceptible to ciprofloxacin, doxycycline and other agents. The use of doxycycline may be preferable to prevent development of ciprofloxacin resistance in more common bacteria. 1 Respiratory transmission of bacillus anthracis from person to person does not occur, so no antimicrobial prophylaxis is indicated.

Closing Facilities

The decision to close a facility is made to prevent cases of inhalation anthrax. The facility should remain closed until the risk for inhalational disease is eliminated.

CDC Interim Guidelines for Investigation of And Response to Bacillus Anthracis Exposures

Environmental Sampling

Directed sampling of environmental surfaces may be indicated:

  • To identify a site or source of bacillus anthracis exposure that has resulted in a case(s) of anthrax

  • To trace the route of an exposure vehicle (e.g., a powder containing letter)

  • To obtain the bacillus anthracis strain when isolates from patients are not available

  • To guide cleanup activities in a contaminated area or building

  • To assess biosafety procedures in laboratories processing bacillus anthracis specimens

Prospective sampling of environmental surfaces may be indicated:

  • To identify receipt of a contaminated exposure vehicle in high risk facilities (e.g., mailrooms of targeted persons or groups)

  • To detect aerosolized bacillus anthracis in high risk areas or events

Laboratory testing of environmental surface samples should not be the only means to determine the need for antimicrobial prophylaxis.

Nasal Swab Cultures

Collection of nasal swabs for culture of bacillus anthracis may be useful:

  • To help define an area of exposure to aerosolized bacillus anthracis
  • To help ascertain where a person with inhalational anthrax was exposed if the time and place of exposure are not already known

Collection of nasal swabs for culture of bacillus anthracis is not indicated:

  • To diagnose anthrax
  • To determine a person's risk of exposure and the need for antimicrobial prophylaxis
  • To determine when antimicrobial prophylaxis should be stopped
  • To supplement random environmental sampling

Antimicrobial Prophylaxis

Antimicrobial prophylaxis may be initiated pending additional information when:

  • A person is exposed to an air space where a suspicious material may have been aerosolized (e.g., near a suspicious powder-containing letter during opening)
  • A person has shared the air space likely to be the source of an inhalational anthrax case

Antimicrobial prophylaxis should be continued for 60 days for:

  • Persons exposed to an air space known to be contaminated with aerosolized bacillus anthracis
  • Persons exposed to an air space known to be the source of an inhalational anthrax case
  • Persons along the transit path of an envelope or other vehicle containing bacillus anthracis that may have been aerosolized (e.g., a postal sorting facility in which an envelope containing bacillus anthracis was processed)
  • Unvaccinated laboratory workers exposed to confirmed bacillus anthracis cultures

Antimicrobial prophylaxis is not indicated:

  • For prevention of cutaneous anthrax
  • For autopsy personnel examining bodies infected with anthrax when appropriate isolation precautions and procedures are followed
  • For hospital personnel caring for patients with anthrax
  • For persons who routinely open or handle mail in the absence of a suspicious letter or credible threat

A positive test for bacillus anthracis from a randomly collected specimen does not require implementation of antimicrobial prophylaxis or the closing of a facility.

Closing a Facility

Closing a facility or a part of a facility may be indicated:

  • After an inhalational anthrax case is detected and a probable site of exposure in the facility is identified
  • When there is a known aerosolization of bacillus anthracis in the facility
  • When evidence strongly suggests an aerosolization of bacillus anthracis in the facility
  • As determined by law enforcement authorities in a criminal investigation

Closing a facility is not indicated:

  • Based only on the identification of bacillus anthracis from samples of environmental surfaces
  • Based only on the identification of a cutaneous anthrax cases

Additional information about anthrax is available at <http://www.hhs.gov/hottopics/healing/biological.html> and < ttp://www.bt.cdc.gov/DocumentsApp/FactsAbout/FactsAbout.asp>.

Additional information about influenza, RSV and other viral respiratory infections, and pneumococcal disease is available at <http://www.cdc.gov/ncidod/diseases/flu/fluvirus.htm>, <http://www.cdc.gov/nip/flu/default.htm>, <http://www.cdc.gov/ncidod/dvrd/revb/index.htm>, <http://www.cdc.gov/ncidod/dbmd/diseaseinfo/streppneum_t.htm>, and <http://www.cdc.gov/nip/diseases/Pneumo/vac-chart.htm>.

References

  1. Interim Guidelines for Investigation of and Response to Bacillus Anthracis Exposures, November 9, 2001 / 50(44);984-6
  2. CDC. Update: investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001. MMWR 2001;50:909--19.
  3. CDC. Update: investigation of bioterrorism-related anthrax and interim guidelines for clinical evaluation of persons with possible anthrax. MMWR 2001;50:941--8.
  4. Nicholson KG. Human influenza. In: Nicholson KG, Webster RG, Hay AJ, eds. Textbook of influenza. Malden, Massachusetts: Blackwell Science 1998:219--64.
  5. Hall CBACILLUS Medical progress: respiratory syncytial virus and parainfluenza virus. N Engl J Med 2001;344:1917--28.
  6. Bartlett JG, Dowell SF, Mandell LA, File TM Jr, Musher DM, Fine MJ. Practice guidelines for the management of community-acquired pneumonia in adults. Clin Infect Dis 2000;31:347--82.
  7. Monto AS. Viral respiratory infections in the community: epidemiology, agents, and interventions. Am J Med 1995;99:6B24S--6B27S.
  8. Carrat F, Tachet A, Rouzioux C, Housset B, Valleron A-J. Evaluation of clinical case definitions of influenza: detailed investigation of patients during the 1995--1996 epidemic in France. Clin Infect Dis 1999;28:283--90.
  9. Monto AS, Gravenstein S, Elliott M, Colopy M, Schweinle J. Clinical signs and symptoms predicting influenza infection. Arch Intern Med 2000;160:3243--7.
  10. Kellogg JA. Culture vs. direct antigen assays for detection of microbial pathogens from lower respiratory tract specimens suspected of containing the respiratory syncytial virus. Arch Pathol Lab Med 1991;115:451--8.
  11. Munoz FM, Galasso GJ, Gwaltney JM, et al. Current research on influenza and other respiratory viruses: II International Symposium. Antiviral Res 2000;46:91--124.
  12. Ryan MAK, Christian RS, Wohlrabe J. Handwashing and respiratory illness among young adults in military training. Am J Prevent Med 2001;21:79--83.